My lab studies the mechanisms governing transgene expression, stem cell engineering, and genetic strategies to enhance immunity against cancer.
The advent of technologies that permit efficient gene transfer in human primary cells creates novel therapeutic perspectives. Based on the use of recombinant oncoretroviruses and lentiviruses, we are investigating how to control transgene expression in vivo in hematopoietic stem cells and how to augment immune responses against tumor cells.
Our current studies on the first topic focus on the role of locus control regions and insulators in regulating the transcription of randomly integrated beta globin transgenes.
With respect to tumor immunity, we are exploring different strategies to target T cells to tumor cells, either by facilitating dendritic cell-T cell interactions or by enhancing the co-stimulation of T cells that engage tumor cells.
Human cells are powerful therapeutic agents. With an expanding array of cell types now under investigation for the treatment of cancer, genetic disorders, infectious diseases, and degenerative disorders, the Center for Cell Engineering (CCE) at Memorial Sloan Kettering Cancer Center is fostering cutting-edge research on emerging cellular therapies.
The CCE brings together researchers who investigate adoptive T cell therapies, bone marrow and cord blood transplantation, human stem cell biology, and the transfer, regulation and repair of genes in human cells. This unique physician scientist partnership comprises researchers from both Memorial Hospital and the Sloan Kettering Institute who strive to devise and implement breakthrough therapies for cancer and allied diseases.
Davila ML, Riviere I, Wang X, Bartido S, Park J, Curran K, Chung SC, Stefanski J, Borquez-Ojeda O, Olszewska M, Qu J, Wasielewska T, He W, Fink M, Shinglot H, Youssif M, Satter M, Wang Y, Hosey J, Quintanilla H, Halton E, Bernal Y, Bouhassira DCG, Arcila ME, Gonen M, Roboz GJ, Maslak P, Douer D, Frattini MG, Giralt S, Sadelain M, Brentjens R. Efficacy and Toxicity Management of 19-28z CAR T Cell Therapy in B Cell Acute Lymphoblastic Leukemia. Sci Transl Med 19 February 2014. Vol. 6, Issue 224, p. 224ra25. DOI: 10.1126/scitranslmed.3008226.
Fedorov VD, Themeli M, Sadelain M. PD-1- and CTLA-4-Based Inhibitory Chimeric Antigen Receptors (iCARs) Divert Off-Target Immunotherapy Responses. Sci Transl Med. 2013 Dec 11;5(215):215ra172. doi: 10.1126/scitranslmed.3006597.
Themeli M, Kloss C, Ciriello G, Fedorov VD, Perna F, Gonen M, Sadelain M. Generation of functional tumor-targeted T lymphocytes from human chimeric antigen receptor-engineered induced pluripotent stem cells. Nat Biotech. 2013 Aug 11.doi: 10.1038/nbt.2678. [Epub ahead of print].
Boulad F, Wang X, Taylor C, Qu Q, Ferro L, Karponi G, Bartido S, Giardina P, Heller G, Prockop SE, Maggio A, Sadelain M, Rivière I. Safe mobilization of CD34+ cells in adults with beta-thalassemia and validation of effective globin gene transfer for clinical investigation. Blood. 2014 Jan 15. [Epub ahead of print]
Brentjens RJ, Davila ML, Riviere I, Park J, Wang X, Cowell LG, Bartido S, Stefanski J, Taylor C, Olszewska M, Borquez-Ojeda O, Qu J, Wasielewska T, He Q, Bernal Y, Rijo IV, Hedvat C, Kobos R, Curran K, Steinherz P, Jurcic J, Rosenblat T, Maslak P, Frattini M, Sadelain M. CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Sci Transl Med. 2013 Mar 20;5(177):177ra38.
Cited in Science magazine “Breakthrough of the Year: Cancer Immunology” (2013)
Sultan Bin Khalifa International Thalassemia Awards (SITA) International Award for Innovative Medical Research on Thalassemia (2013)
Elected to Vice President of the American Society for Gene and Cell Therapy (Vice President 2013, President Elect 2014, President 2015)
Antonio Cao Award for Research in Thalassemia or Hemoglobinopathies, Palermo, Italy (2013)
Recipient of the Coley Award of the Cancer Research Institute for Distinguished Research in Tumor Immunology (shared with Carl June, University of Pennsylvania) (2012)
Member, Grant Review Committee and Strategic Committee, CIRM (2011)
Incumbent of the Stephen and Barbara Friedman Chair (2007)
V Foundation Award in Honor of Mayor Rudolph Guliani (2005)